Marked increases in the rate of uptake of substrates (methylaminisobutyric acid, MeAIB, and aminoisobutyric acid, AIB) of the Na+ energy-dependent System A occurred during exponential growth in several cell culture lines and in thymus lymphocytes after stimulation with mitogenic agents or amino acid deprivation. Irrespective of the cell type or mechanism of stimulation, indomethacin and other anti-inflammatory drugs suppressed this increase without altering the affinity of the uptake system for the MeAIB or Na+ ions. This inhibition was observed in thymus lymphocytes removed from rats given pharmacological doses of indomethacin. The early part of the cell cycle appears to be uniquely sensitive to the action of anti-inflammatory drugs in that, once DNA synthesis has commenced in cell cultures, indomethacin no longer suppresses mitogenesis. The data suggest that the Na+ dependent components of MeAIB transport in both the thymus lymphocytes and cell culture lines share common features and interact with nonsteroidal anti-inflammatory drugs in a similar manner.